U.S. Pat. No. 5,660,691 describes a process for the production of tocotrienol/tocopherol blend concentrates from vegetable oil by-products such as deodorizer distillates, steam refining distillates, acidulated soapstock and other vegetable oil by-products rich in tocotrienol. U.S. Pat. No. 6,224,717 discloses solvent/water mixtures in connection with the separation of tocotrienol from tocol-containing mixtures. According to U.S. Pat. No. 6,224,717, DE 3615029 discloses the purification of tocopherols by contacting a tocopherol containing substance with neat methanol to form two layers, separating the methanol layer, cooling the methanol layer to produce a methanol phase and a raffinate layer, and recovering the tocopherols from the methanol layer. A disadvantage of this method is that a considerable amount of tocopherols are lost to the raffinate, thereby reducing the overall recoverable yield. U.S. Pat No. 4,550,183 discloses extracting a tocopherol containing material with caustic methanol to produce a two-phase system. The methanol layer is removed and neutralized with acid. A disadvantage of this method is that an additional step is required to neutralize the basic methanol layer. JP 03127730 A discloses extracting an unsaturated oil or fat with a neat extraction solvent composed of neat butanol, ethylene glycol, methyl ethyl ketone, acetone, benzene, or cyclohexane followed by a series of distillation steps.
Published U.S. Patent Application No. 20020142083 entitled Process for the Production of Tocotrienols uses “solvent wintering” as a process step in the preparation of tocotrienols. Wintering is the cooling of oil, with or without added solvent, to effect the crystallization of sterols and sterol like materials.
The prior art pertaining to processes for separating or recovering components of vegetable oil sources includes U.S. Pat. No. 6,552,208; WO 200151596, Isolation of Non-Saponifiables from Vegetable Oils; EP 1097985 (Chemical Abstracts 2325224), Chromatographic Isolation for Non-Glyceride Components; Chang, Chiehming J. et al., Supercritical Carbon Dioxide Extraction of High-Value Substances from Soybean Oil Deodorizer Distillate, Industrial & Engineering Chemistry Research (2000), 39 (12), 4521-4525; Binder, Thomas P., ADM Research, Processing Deodorizer Distillate for Value-Added Products, Abstracts of Papers, 225th ACS National Meeting, New Orleans, La. Mar. 23-27, 2003, AGFD-113, American Chemical Society.
The outer-most layer of human skin, the stratum corneum, provides the barrier function of the skin, preventing dehydration of underlying tissues and preventing absorption of various undesirable substances into the body. The stratum corneum consists of dead cells that are surrounded by proteins and lipids. It is primarily the lipid layer that provides the barrier function of the skin. Both squalene and sterols (predominately cholesterol) are natural components of the stratum corneum lipid layer. See, for example, De Paepe, Kristien, Cosmetic Lipids and the Skin Barrier, Foerster, Thomas, Ed. Marcel Dekker: New York, 2002; pages 152-153). Squalene is a major component of sebum secreted by the sebaceous glands (Moller, Hinrich, Cosmetic Lipids and the Skin Barrier, p 5). The benefits of lipids in cosmetics are discussed in detail by Lanzendorfer, Ghita in Cosmetic Lipids and the Skin Barrier, pages 271-290).
Several patents cite the use of the various components of lipid compositions, individually and in combinations with one another, to provide benefits to the skin, including the lips, or to the personal care product itself. U.S. Pat. No. 6,306,898 (WO 9632933) describes four aspects of preparations for treating dermatoses. The third aspect comprises a nonsteroidal anti-inflammatory agent, vitamin E, and squalane and/or squalene. The fourth aspect comprises an antihistaminic agent, vitamin E, and squalane and/or squalene. The vitamin E in combination with squalane or squalene is described as having a synergistic therapeutic effect in cooperation with the nonsteroidal anti-inflammatory agent or antihistaminic agent, respectively.
U.S. Pat. No. 5,494,657 describes the use of compositions comprising petrolatum, squalene or hydrogenated polybutene, non-hydrogenated polybutene, a fatty acid or fatty acid ester, and an antioxidant for moisturizing skin. The antioxidant is described as comprising a natural or synthetic alpha-tocopherol. One object of U.S. Pat. No. 5,494,657 is to provide skin care compositions similar to natural sebum. This patent teaches that the combination of polybutenes, the fatty acid or fatty acid ester, and anti-oxidant provides a balanced formulation which protects the skin while allowing controlled oxygen permeability. U.S. Pat. No. 5,378,461 describes a composition for topical treatment of damaged skin comprising a carrier solution consisting of squalene or squalane, a ubiquinone (coenzyme Q), and vitamins E, A, and D. Squalane and squalene have been shown to be a very effective transport medium for the other ingredients. U.S. Pat. No. 5,378,461 teaches that squalene is a natural emollient since it is synthesized in the sebaceous glands and Vitamin E is known to serve as an antioxidant—reducing or eliminating lipid peroxidation.
U.S. Pat. No. 4,454,159 describes preparations for the treatment of irritated, pruritic, and dry skin conditions that contain glycerol trioleate, a glyceride oil, hydrogenated glyceride oil, lecithin, tocopherol, a humectant, isopropyl palmitate, squalene or squalane, and a collagen product. The lipids used in the preparations should be rich in tocopherol. The compositions of U.S. Pat. No. 4,454,159 were found to exhibit unusual skin therapy in their ability to relieve skin irritation and itching. WO 2002026207 describes a cosmetic formulation that is characterized by a lipid composition comprising squalene which approximates human sebum. The compositions also contain natural vitamin E acetate. JP 09169638 describes a composition for treating dermatological diseases containing astringent (0.9-50%), vitamin E (0.1-99%), and squalane and/or squalene (0.1-99%). The astringent is preferably tannic acid, zinc oxide, or potassium aluminum sulphate. Patents that mention both squalene and vitamin E (or tocopherol) as ingredients in skin care formulations, refer to them as optional ingredients or include them in long lists of optional components. The prior art does not attribute any particular benefit to the combination of squalene and tocopherol in skin care formulations.
The following publications pertain to the use of sterols or phytosterols in skin care applications. U.S. Pat. No. 6,534,074 describes a composition applied to “a body facing material” that enhances skin barrier properties. The composition comprises natural fats or oils, sterols or sterol derivatives, a surfactant, a humectant, an emollient, a wax, and an oil soluble or dispersible viscosity enhancer. The specific benefit of including sterols or sterol derivatives in the formulation is not discussed. Rice bran wax is not included in the list of waxes that can be used as the wax component.
U.S. Pat. No. 6,284,802 describes a method for regulating the condition of mammalian keratinous tissue by applying a composition comprising farnesol, other skin care actives, and a carrier. Antioxidant and anti-inflammatory agent are listed as possible skin care actives. The antioxidant is selected from a group that includes tocopherol; and the anti-inflammatory agent is selected from a group that includes phytosterol. U.S. Pat. No. 6,153,209 describes an article for applying a skin care composition to the skin. The skin care composition is further described as comprising an emollient, a permeability agent, and an immobilizing agent. Sterols and sterol esters are included in the list of possible emollients; squalene is included in the list of possible permeability agents; and wax is included in the list of immobilizing agents. Rice bran wax is not included in the list of waxes that are specifically mentioned as possible waxes. The skin care composition can further comprise an antioxidant selected from a group that includes tocopherols and mixed tocopherols.
U.S. Pat. No. 5,882,660 describes a personal care composition in the form of an aqueous liquid comprising a lipid composition, a surface-active agent, and a cationic polymer. The lipid composition comprises two components, one of which is selected from a group that includes 3-beta-sterol and squalene. Examples of 3-beta-sterols include cholesterol, sitosterol, stigmasterol and ergosterol. This patent discloses that cholesterol is a vital component of the natural skin lipids that constitute the moisture barrier in the stratum corneum. U.S. Pat. No. 5,733,572 (WO 9109629) describes a gas filled lipid-containing microsphere comprising a therapeutic agent or cosmetic for topical application. Among the many components that can make up the composition are vitamins, including vitamin E; ointment bases including squalene; and a biocompatible lipid, including cholesterols, tocopherols, and non-ionic lipids.
U.S. Pat. No. 5,688,752 describes an aqueous liquid personal care cleansing composition comprising three components. One of the components is selected from a group that includes 3-beta-sterol and squalene. EP 467218 describes a lipid composition for cosmetics comprising fatty acids and/or their tocopheryl esters (0-95%), n-alkanes (0-65%), squalene (0-30%), cholesterol and/or lanolin alcohol (0-50%), triglycerides (0-80%), and/or wax esters (0-60%), where at least 2 of these components must be present. Also described is a skin oil containing the above lipid composition (10%).
Both U.S. Pat. No. 4,218,334 and U.S. Pat. No. 6,087,353 discuss the problem of solubilizing or dispersing phytosterols in emulsions and other formulations. U.S. Pat. No. 4,218,334 proposes that this problem may be solved by making a blend of phytosterol with free fatty acids or saturated free fatty alcohols. U.S. Pat. No. 6,087,353 proposes a solution to the problem which includes esterifying, then hydrogenating, the phytosterol. U.S. Pat. No. 6,087,353 also discusses the need to enhance the stability of phytosterol compositions.
The following publications pertain to the use of lipid compositions in food, nutritional, and pharmaceutical applications. U.S. Pat. Nos. 5,952,393 and 6,197,832 describe compositions and method for reducing serum cholesterol in humans and animals. The method comprises administering phytosterol and policosanol which together produce a synergistic effect in lowering serum cholesterol levels. Preferably, the administered composition includes about 3.2:1 parts by weight of phytosterol and policosanol. U.S. Pat. No. 6,025,348, U.S. Pat. No. 6,139,897 and U.S. Pat. No. 6,326,050 describe oil or fat compositions comprising 15 or more weight percent of a diacylglycerol and 1.2 to 20 weight percent phytosterol dissolved or dispersed in the fat and oil. U.S. Pat. No. 6,087,353 provides an esterified and subsequently hydrogenated phytosterol composition for use alone or for incorporation into foods, beverages, pharmaceuticals, nutraceuticals, and the like. The composition has the advantage of enhanced solubility/dispersibility, increased molar potency and enhanced stability over naturally isolated phytosterol compositions. Methods for the esterification and subsequent hydrogenation of the phytosterols are also provided.
U.S. Pat. No. 6,204,290 pertains to novel tocotrienols and tocotrienol-like compounds that exhibit biological activity. This patent discloses that the tocotrienols and tocotrienol-like compounds may be conveniently obtained from biological sources or by chemical synthesis and may be used in pharmaceutical compositions, foodstuffs and dietary supplements. U.S. Pat. No. 6,204,290 also discloses the use of tocotrienols, tocotrienol-like compounds, and mixtures thereof, as hypocholesterolemic, antithrombotic, antioxidizing, antiatherogenic, antiinflammatory and immunoregulatory agents, or as agents useful to decrease lipoprotein (a) concentration in the blood or to increase feed conversion efficiency.
U.S. Pat. No. 6,277,431 describes an edible oil that decreases the synthesis, absorption and blood level of cholesterol by a human patient, increases the excretion of cholesterol from the human patient, curtails accumulation of peroxidized material in the blood of the human patient, and also increases the blood level of vitamin E in said human patient. The edible oil is comprised of about 10 to 30% tocopherols, tocotrienols or combinations thereof; about 2 to 20% free sterols; about 2 to 20% sterol esters; about 0.1 to 1.0% of cycloartenols; and; about 7 to 19% of saturated fats, wherein all percentages are weight/weight.
Sterols are naturally occurring triterpenoids that perform many critical cellular functions, and so phytosterols have received a great deal of attention due to their ability to decrease serum cholesterol levels when fed to a number of mammalian species, including humans. Phytosterols such as campesterol, stigmasterol and beta-sitosterol in plants, ergosterol in fungi and cholesterol in animals are each primary components of cellular and sub-cellular membranes in their respective cell types. The dietary source of phytosterols in humans comes from plant materials i.e. vegetables and plant oils. The estimated daily phytosterol content in the conventional western-type diet is approximately 60-80 milligrams in contrast to a vegetarian diet that provides about 500 milligrams per day.
Plant constituents have been proven useful in the prevention and treatment of a wide variety of diseases and conditions. Recent studies have indicated that tocotrienols may be biologically active. For example, U.S. Pat. No. 4,603,142 identifies d-alpha-tocotrienol, isolated from barley extracts, as an inhibitor of cholesterol biosynthesis. See also A. A. Qureshi et al. (1986), supra. Various human and animal studies have confirmed the impact of pure tocotrienols, isolated from barley, oats and palm oil, on cholesterol biosynthesis, specifically LDL-cholesterol (A. A. Qureshi et al., Dietary Tocotrienols Reduce Concentrations of Plasma Cholesterol, Apolipoprotein B, Thromboxane B. sub.2 and Platelet Factor 4 In Pigs With Inherited Hyperlipidemias, Am. J. Clin. Nutr., pp. 1042S-46S (1991); A. A. Qureshi et al., Lowering Of Serum Cholesterol In Hypercholesterolemic Humans By Tocotrienols (Palmvitee), Am. J. Clin. Nutr., 53, pp. 1021S-26S (1991); D. T. S. Tan et al., The Effect Of Palm Oil Vitamin E Concentrate On The Serum And Lipoprotein Lipids In Humans, Am. J. Clin. Nutr., 53, pp. 1027S-30S (1991)).
Other chromanols, the tocopherols, including d-α-tocopherol (vitamin E), have been extensively studied. As a result of these studies, certain biological activities have been attributed to the tocopherols. Such activities include platelet aggregation and antioxidant functions—see, for example, E. Niki et al., Inhibition of Oxidation of Biomembranes By Tocopherol, Annals of the New York Academy of Sciences, 570, pages 23-31 (1989) and K. Fukuzawa et al., Increased Platelet-Activating Factor (PAF) Synthesis in Polymorphonuclear Leukocytes of Vitamin E-Deficient Rats, Annals of the New York Academy of Sciences, 570, pages 449-453 (1989)). Although the exact structure-function relationship is not known, several experiments have highlighted the importance of the phytyl side chain in the biological activity of tocopherols. See W. A. Skinner et al., Antioxidant Properties of .alpha.-Tocopherol Derivatives and Relationships of Antioxidant Activity to Biological Activity, Lipids, 5(2), pp. 184-186 (1969) and A. T. Diplock, Relationship of Tocopherol Structure to Biological Activity, Tissue Uptake, and Prostaglandin Biosynthesis, Annals of the New York Academy of Sciences, 570, pp. 73-84 (1989)).